Add like
Add dislike
Add to saved papers

Pyrrolizidine Alkaloid Secondary Pyrrolic Metabolites Construct Multiple Activation Pathways Leading to DNA Adduct Formation and Potential Liver Tumor Initiation.

Pyrrolizidine alkaloids (PAs) and their N-oxide derivatives are hepatotoxic, genotoxic, and carcinogenic phytochemicals. PAs induce liver tumors through a general genotoxic mechanism mediated by a set of four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-derived DNA adducts. To date, the primary pyrrolic metabolites dehydro-PAs, their hydrolyzed metabolite DHP, and two secondary pyrrolic metabolites 7-glutathione-DHP (7-GS-DHP) and 7-cysteine-DHP are the known metabolites that can generate these DHP-DNA adducts in vivo and/or in PA-treated cells. Secondary pyrrolic metabolites are formed from the reaction of dehydro-PAs with glutathione, amino acids, and proteins. In this investigation, we determined whether or not more secondary pyrrolic metabolites can bind to calf thymus DNA and to cellular DNA in HepG2 cells resulting in the formation of DHP-DNA adducts using a series of secondary pyrrolic metabolites (including 7-methoxy-DHP, 9-ethoxy-DHP, 9-valine-DHP, 7-GS-DHP, 7-cysteine-DHP, and 7,9-diglutathione-DHP) and synthetic pyrroles for study. We found that (i) many secondary pyrrolic metabolites are DNA reactive and can form DHP-DNA adducts and (ii) multiple activation pathways are involved in producing DHP-DNA adducts associated with PA-induced liver tumor initiation. These results suggest that secondary pyrrolic metabolites play a vital role in the initiation of PA-induced liver tumors.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app